Molecular Mechanism of Dual Intercalation in Sac7d–DNA Complexation

Sac7d belongs to the hyperthermophilc chromosomal protein family, and it is very stable with regard to heat and acidic environments. Unlike many other DNA–protein complexes, the present one is a nonspecific complexation where two amino acids (AA), VAL26 and MET29, are found to intercalate into the same base pair of DNA. Here, we have carried out multiple short molecular dynamic simulations to calculate the distribution of nonspecific protein–DNA aggregates to find the most probable state, which was subsequently used to construct the free energy landscape of protein intercalation into DNA. Analysis of trajectories along the minimum free energy path revealed mechanistic details such as rotation of the protein, simultaneous intercalation of two amino acids, and bending/kinking of the DNA. Moreover, the results indicate a strong interdependency between the intercalating amino acids such that the deintercalation of one AA leads to a spontaneous deintercalation of the other.